Craniofacial and dental defects have devastating effects on patients not only because vital sense organs and the brain are housed within the cranium, but also because our face represents an important aspect of our identity. Furthermore, such defects can lead to compromised general health. In recent years, stem cells combined with sophisticated scaffolds have shown promise as bio-inspired solutions to biological problems in dental, oral, and craniofacial regenerative medicine. Our vision is to assemble a comprehensive team of clinicians, research scientists, biostatisticians, regulatory science and pre-clinical/clincal trial experts to enable the development and clinical implementation of innovative approaches for dental, oral, and craniofacial tissue regeneration. Towards this end, we will develop a multi-institutional Center for Dental, Oral, and Craniofacial Tissue and Organ Regeneration (C-DOCTOR) that is driven by clinical needs, as defined by practicing clinicians. In Specific Aim 1, we will assemble a team of experts with integrated clinical, scientific/technical, and regulatory science expertise required to form the C-DOCTOR and enable us to successfully develop, manufacture, and apply mesenchymal stem cell-mediated tissue regeneration therapies. The team will evolve based on newly identified clinical and research opportunities. We will host two working retreats and monthly teleconferences to develop and refine the overall vision, roadmap, organizational structure, and operational procedures for the C-DOCTOR. The capacity of our center will match public needs in order to provide clinical benefits for patients. In Specific Aim , we will enable clinicians to define clinical needs for craniofacial tissue and organ regeneration, and to engage with research scientists to assess feasibility. According to these needs, we will develop the necessary technical approaches, statistical methods, manufacturing and quality control procedures, vertebrate animal protocols, and human subject protections. In support of this aim, we will develop a website to foster communications with the public, potential interdisciplinary translational project teams, and other resource centers funded through this RFA throughout the nation. Ultimately, our collective expertise at the C-DOCTOR will provide comprehensive services to meet patient needs for tissue regeneration by establishing well-defined procedures for successful experimental design, large animal models, product validation, manufacturing scale-up, regulatory approval, clinical testing, and implementation.